Primary ciliary dyskinesia (PCD) is an umbrella term for inherited disorders of the cilia, complex organelles that are outgrowths on the surfaces of cells lining the upper and lower and respiratory tracts. Each cell contains approximately 200 cilia that normally beat very fast in a coordinated fashion to enable mucus (inhaled particles and germs) to be cleared from the lungs, sinuses, and middle ear. Impaired ciliary function alters this mucociliary clearance and results in recurrent pneumonia, chronic sinus infection, and persistent otitis media. In addition to chronic respiratory disease, people with PCD may have abnormalities in the placement of internal organs (laterality) and reduced fertility.
The diagnosis of PCD is often delayed in children with clinical features of chronic respiratory tract infections due to overlap with other common childhood respiratory diseases, including cystic fibrosis, immunodeficiency, asthma, aspiration, and recurrent respiratory viral infections. Clinical features most common to patients with PCD include: 1) year-round, daily productive cough (nearly 100%); 2) year-round daily rhinosinusitis (nearly 100%); 3) neonatal respiratory distress (close to 75%); and 4) organ laterality (approximately 50%). In addition, diagnosis may be delayed due to the limitations of available diagnostic tests.
The 2018 ATS Clinical Practice Guideline focuses on the diagnosis of PCD and provides a suggested diagnostic algorithm for evaluating the patient with suspected PCD and incorporates genetic testing, electron microscopy of ciliary ultrastructure obtained from ciliary biopsy, and nasal nitric oxide (nNO) measurements. More than 40 genes have been associated with PCD, and the current genetic panels may provide a diagnostic yield of 70-75%. Although ultrastructural abnormalities in cilia obtained by biopsy can be diagnostic for PCD and has been the mainstay of diagnosis for nearly 4 decades, the absence of ultrastructural defects in 30% of patients and challenges in obtaining an adequate biopsy have resulted in significant limitations; thus, a normal biopsy does not rule out PCD. For reasons still not understood, levels of nNO remain very low in patients with PCD. This measurement is not an FDA-approved method for the diagnosis of PCD but may be useful at a clinical site that is part of the PCD Foundation Clinical and Research Centers Network.
Treatment for PCD requires multidisciplinary monitoring for progression of lung and sinus disease and utilizes airway clearance and antibiotics to treat underlying infections. The cycle of chronic inflammation and infection may result in bronchiectasis and decline in pulmonary function testing in patients with PCD.
Current and future priorities in PCD include improved case recognition and diagnosis, infrastructure for multicenter studies, and discovery of the pathogenesis of many forms of PCD, including the underlying genetic mechanisms. There is a critical unmet need to develop and test therapies for PCD. The PCD Foundation has facilitated a multicenter, interdisciplinary group of providers and investigators to advance the field including through improved classification, phenotyping, and a longitudinal Registry in the United States. The American Thoracic Society and the PCD Foundation continue to advocate to increase awareness, facilitate education of families and providers, and promote research needed to accelerate progress to improve the lives of children and families affected by PCD.
Paul E. Moore, MD, ATSF
Professor of Pediatrics and Pharmacology
Vanderbilt University School of Medicine
Four Facts About Primary Ciliary Dyskinesia
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